Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE)

This study has been terminated.

(commitment completed)

Sponsor:

Cubist Pharmaceuticals LLC

ClinicalTrials.gov Identifier:

NCT00638157

First Posted: March 18, 2008

Last Update Posted: January 7, 2016

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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multicenter, randomized, double blind study to describe the safety and efficacy of daptomycin (6 mg/kg q24h) with and without concomitant initial gentamicin combination therapy in the treatment of SAIE

A Phase 4 Multicenter, Randomized, Double Blind Study to Describe the Efficacy and Safety of Cubicin® (Daptomycin for Injection) With and Without Initial Gentamicin Combination Therapy in the Treatment of S. Aureus Infective Endocarditis

The End of Treatment (EOT)/Early Termination (ET) visit occurred on the day that therapy was stopped or up to 2 days after the last dose of daptomycin. The Test of Cure (TOC)/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. The overall median duration of treatment was 13.0 days in both the daptomycin group and the combination therapy group. The definition of elevated serum creatinine at baseline is >3.0 mg/dL, and not elevated is ≤3.0 mg/dL. Clinically significant increases in serum creatinine is defined as an increase ≥0.5 mg/dL for patients with a baseline value ≤3.0 mg/dL or ≥1.0 mg/dL for patients with a baseline value >3.0 mg/dL.

Secondary Outcome Measures:

Summary of the Investigator's Assessment of Clinical Response at the TOC Visit [ Time Frame: TOC Visit ]

TOC/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. Clinical response was assessed by the investigator as cure, improvement, failure, and unable to evaluate. Microbiological response, which was determined by the sponsor based on review of baseline and post-baseline culture results, included success, failure, and nonevaluable. TC=Treatment Cure; TF=Treatment Failure; TI=Treatment Improved.

daptomycin 6 mg/kg q24h with concomitant initial gentamicin dosed for the first 2 days of therapy for the treatment of right-sided infective endocarditis

Drug: daptomycin and gentamicin

i.v. daptomycin 6 mg/kg q24h plus initial i.v. gentamicin

Other Names:

Cubicin

daptomycin for injection

gentamicin

Detailed Description:

Patients will be randomized to either of the following two treatment arms:

Arm 1: daptomycin

Arm 2: daptomycin with initial i.v. gentamicin

Patients who meet all the inclusion criteria and exhibit none of the exclusion criteria may be enrolled. Intravenous drug user (IVDU) patients may be randomized and study drug begun on the basis of two separate peripheral blood cultures positive for S. aureus obtained within 96 hours prior to the first dose of study drug.

The recommended minimum duration of treatment for daptomycin will be 28 days. The duration of treatment for gentamicin will be 3 days.

During study treatment, regular assessments (including weekly safety laboratory testing including CPK) will be performed. An End-of-Therapy (EOT) evaluation will be performed on the day of or 1-2 days after completion of daptomycin study drug or upon early termination (ET). All patients will have a post-therapy visit for Test of Cure (TOC)/Safety performed 21-28 days following the last dose of daptomycin study drug.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Written informed consent has been obtained;

Male or female ≥18 years of age;

IVDU (as confirmed by history of drug abuse within the past 3 months or recent needle track marks);

Two blood cultures positive for S. aureus obtained within 96 hours prior to first dose of study medication acquired by fresh venipuncture using aseptic technique and analyzed at the local laboratory (see Appendix B).

Exclusion Criteria:

Intravascular foreign material in place at the time that the positive blood culture was drawn (e.g., intracardiac pacemaker wires, percutaneous or implanted venous catheters, vascular grafts), (exception: vascular stents that have been in place for >6 months or permanent pacemaker wires attached via epicardial leads are allowed);

Findings on screening examination of major systemic emboli to visceral organs (e.g. cerebral or splenic infarct). Patients may be included if their only findings are consistent with microvascular phenomena due to immune complexes (e.g., splinter hemorrhages, conjunctival petechiae, Roth's spots, Osler's nodes, Janeway's lesions, microhematuria).

Note: Any patient enrolled in the study that is subsequently found to have LIE may be continued in the trial if determined to be clinically improving by the Investigator.

Anticipated to require non-study antibiotics that may be potentially effective against S. aureus;

Prior gentamicin therapy > 1 day;

Documented history of significant allergy or intolerance to any of the study medications;

Unlikely to comply with study procedures;

Pregnant or nursing. All females with childbearing potential will have a pregnancy test performed at the local laboratory.

Female of childbearing potential and not willing to practice barrier methods of birth control (e.g., condoms or diaphragms together with spermicidal foam or gel) during treatment and for at least 28 days after treatment with study medication

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00638157